PMID- 9554971 OWN - NLM STAT- MEDLINE DCOM- 19980723 LR - 20190614 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 788 IP - 1-2 DP - 1998 Mar 30 TI - Regulation of G protein-mediated adenylyl cyclase in striatum and cortex of opiate-dependent and opiate withdrawing mice. PG - 104-10 AB - Previous research has demonstrated that acute and chronic opiate treatment alters receptor- and postreceptor-mediated adenylyl cyclase activity. This study examined the regulation of G protein- and forskolin-mediated adenylyl cyclase activity in mouse striatum and cortex after short- and long-term opiate exposure. To directly measure adenylyl cyclase enzymatic activity, assays were done in the presence of catalytic site activator forskolin. To measure G protein-mediated adenylyl cyclase activity, assays were performed in the presence of non-hydrolyzable guanosine 5'-triphosphate (GTP) analogue, 5'-guanylyl-imidodiphosphate. Short-term in vitro morphine exposure produced reductions in forskolin-stimulated adenylyl cyclase activity in striatal and cortical tissues. Long-term morphine treatment in mice was performed via morphine- or placebo-pellet implantation for 72 h; this treatment has been shown to produce opiate dependence and withdrawal. In both opiate-dependent and opiate withdrawing mice (1 h post-naloxone induction), there were significant increases in G protein-mediated adenylyl cyclase activity in the striatum (vs. controls). In opiate-dependent mice, there was an decrease in G protein-mediated adenylyl cyclase activity in cortex. In opiate-dependent mice, there were no changes in forskolin-stimulated adenylyl cyclase in the striatum or cortex. Increases in striatal G protein-mediated adenylyl cyclase could represent a compensatory adaptation that opposes the persistent inhibition of adenylyl cyclase by chronic opiate treatment contributing to the expression of opiate dependence and withdrawal. CI - Copyright 1998 Elsevier Science B.V. FAU - Kaplan, G B AU - Kaplan GB AD - Department of Psychiatry and Human Behavior, Veterans Affairs Medical Center and Brown University School of Medicine, Providence, RI 02908, USA. FAU - Sethi, R K AU - Sethi RK FAU - McClelland, E G AU - McClelland EG FAU - Leite-Morris, K A AU - Leite-Morris KA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 1F7A44V6OU (Colforsin) RN - 76I7G6D29C (Morphine) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 4.6.1.1 (Adenylyl Cyclases) SB - IM MH - Adenylyl Cyclases/*metabolism MH - Analysis of Variance MH - Animals MH - Cerebral Cortex/drug effects MH - Colforsin/pharmacology MH - Corpus Striatum/drug effects MH - GTP-Binding Proteins/*physiology MH - Logistic Models MH - Male MH - Mice MH - Mice, Inbred Strains MH - Morphine/*adverse effects MH - Morphine Dependence/*enzymology MH - *Substance Withdrawal Syndrome MH - Telencephalon/*drug effects/enzymology EDAT- 1998/05/21 00:00 MHDA- 1998/05/21 00:01 CRDT- 1998/05/21 00:00 PHST- 1998/05/21 00:00 [pubmed] PHST- 1998/05/21 00:01 [medline] PHST- 1998/05/21 00:00 [entrez] AID - S0006-8993(97)01524-2 [pii] AID - 10.1016/s0006-8993(97)01524-2 [doi] PST - ppublish SO - Brain Res. 1998 Mar 30;788(1-2):104-10. doi: 10.1016/s0006-8993(97)01524-2.